5. The physiologic mechanism for
CINV
Chemotherapy stimulates the Chemoreceptor Trigger
Zone (CTZ) directly.
Chemotherapy stimulates enterochromaffin cells in the
GI tract to release serotonin.
Serotonin activates 5-HT3 receptors in 3 areas: vagal
afferents in the GI tract, Nucleus Tractus Solitarius
(NTS), and the CTZ
Dopamine-2, histamine, and neurokinin-1 receptors are
stimulated.
Impulses feed into the VC.
When a threshold is reached in the VC, nerve impulses
are carried by efferent nerves to stimulate emesis.
5
6. Neurotransmitters and the
reseptor targets
Serotonin and serotonin type 3 (5-HT3)
resceptor
Dopamine and dopamine type 2 receptor
Substance P and neurokinin-1 or NK
receptor
Histamine, acetylcholin, opiates and
respective receptor
6
8. TWO PHASE of CINV
Acute phase
occure in first 24 hour and is mediated by
release of serotonin from enterochromaffin
cells within GI tract
Deleyed phase
- occure during 24 hour periode post
chemoterapy until 72 hour
- Including cisplatin, carboplatin,
cyclophosphamid,
and antracyclines (eq. doxorubicine,
epirubicin)
8
11. Asses the Emetognicity
of the combination
Level 1 agents do not contribute to the
emetogenicity of a given regimen.
Adding one or more level 2 agents increases
emetogenicity of the combination by one level
greater than the most emetogenic agent in the
combination.
Adding level 3 and 4 agents increases
emetogenicity of thecombination by one level
per agent.
11
12. A
Level 1
B
Level 2
C
Level 3
Level
Kombinasi ?
A
Level 3
A
Level 3
A
Level 2
A
Level 2
Level
Kombinasi ?
A
Level 2
A
Level 2
A
Level 3
A
Level 4
Level
Kombinasi ?
Contoh
12
14. Antiemetic Regimen for prophylaxis of CINV
Acut Nausea Vomoting
(first 24 hours)
Deleyed Nausea/Vomiting
(day 2-5)
Emetic potensial : High (level5)/freguency of emesis > 90 %
Cisplatin agent
5HT-3 antagonist + Corti costeroid +
apripitant (all single dose 30-60 minute
befor chemotheraphy)
Noncisplatin agent
5HT-3 + Corticosteroid ± apripitant (all
single dose 30-60 minute befor
Cisplatin agent
1. Apripitant + corticosteroid
2. One of noncisplatin
agent
Noncicplatin agent
1. Apripitant+corticosteroid (if apripitant
used on day 1)
2. Corticosteroid (single agent)
3. Metoclopropamid + Corticosteroid
4. 5HT-3 antagonis + Corticosteroid
Emetic potensial : High (level 4)/freguency of emesis 60 - 90 %
5HT-3 antagonis + Corti costeroid ±
apripitant (all single dose 30-60 minute befor
chemotheraphy
1. Apripitant + corticosteroid (if apripitant
used on day 1)
2. Corticosteroid (single agent)
3. Metoclopropamid + Corticosteroid
4. 5HT-3 antagonis + Corticosteroid
5. (1-4) without corticosteroid
14
15. Antiemetic Regimen for prophylaxis of
CINV
Acut Nausea Vomoting
(first 24 hours)
Deleyed Nausea/Vomiting
(day 2-5)
Emetic potensial : High (level 3)/freguency of emesis > 30 - 60 %
5HT-3 antagonis + Corticosteroid 1. Corticosteroid (single agent)
2. Metoclopropamid + Corticosteroid
3. 5HT-3 antagonis + Corticosteroid
Emetic potensial : High (level 2)/freguency of emesis 10 - 30 %
1. Corticosteroid (single dose 30 minute
befor chemotheraphy)
2. Dopaminergic antagonist (single dose
30 minute befor chemotheraphy)
Note : Antiemetic premedication often not
necessary
Not necessary
Emetic potensial : High (level 1)/freguency of emesis < 10 %
Antiemetic remedication ussually not
necessary
Not necessary
15
16. Dosing Recommendation for CINV Prophylaxi
(Adults)
for Moderate to Highly Emetic Chemotherapy
(level 3–5)
Agent
Acut CINV Prophylaxis (day 1)
(single dose given 30 minutes
before chemotherapy)
Deleyed CINV
Prophylaxis
(days 2-5)
Tablet/Caps Size
for Oral
Administration
Oral (po) Intravenous (iv)
5HT3 Receptor Antagoists
Dolasetron 100-200 mg po 100 mg or 1.8
mg/kg IV
100-200 mg po
daily x 2-4 days
50 mg, 100 mg
Granisetron 2 mg po 10 mg/kg IV 1 mg po twice
daily x 2-4 days
1 mg
Ondansetron 24 mg po 8 mg or 0,15
mg/kg iv
8 mg po twice
daily x 2-4 days
4, 8 mg
Palanosetron NA 0,25 mg iv NA
Because of its extended half-life palonosetron should be given only on day 1, Repeat doses within a
7-day interval are not recommended. Efficacyin prevention of deleyed CINV has been demontrated
after the day 1 dose in moderately ematogenic chemotherapy
16
17. 17
Agent
Acut CINV Prophylaxis (day 1)
(single dose given 30 minutes
before chemotherapy)
Deleyed CINV
Prophylaxis
(days 2-5)
Tablet/Caps
Size for Oral
Administration
Oral (PO) Intravenous (IV)
Corticosteroids
Dexamethasone
phosphate
(Decadron)
8–20 mg PO 8–20 mg IV 4 mg twice daily
or 8 mg PO daily
or 8 mg twice
daily for 2–4
days
0,5 mg ; 0,75 mg
Methylprednisolo
ne sodium
succinate
(Solu-Medrol)
NA 40–125 mg IV NA NA
• For highly emetogenic chemotherapy, dexamethasone doses of 20 mg have been shown to
be more efficacious than lower doses. In moderately emetogenic chemotherapy, doses
greater than 8 mg have not been shown superior to an 8-mg dose
• When combined with aprepitant, IV doses of dexamethasone should be reduced by 25%,
and PO doses of dexamethasone should be reduced by 50%. A 12-mg dose of
dexamethasone for acute prophylaxis in combination with aprepitant is the only
dexamethasone dose evaluated in large randomized trials
18. 18
Agent
Acut CINV Prophylaxis (day 1)
(single dose given 30 minutes
before chemotherapy)
Deleyed CINV
Prophylaxis
(days 2-5)
Tablet/Caps
Size for Oral
Administration
Oral (PO) Intravenous (IV)
NK1 Receptor Antagonists
Aprepitant
(Emend)
125 mg PO NA 80 mg PO daily
for 2 days
80 mg, 125 mg
Fosaprepitant
(Emend)
NA 115 mg ; 150
mg IV
NA NA
19. Agent
Acut CINV Prophylaxis (day 1)
(single dose given 30 minutes
before chemotherapy)
Deleyed CINV
Prophylaxis
(days 2-5)
Tablet/Caps Size
for Oral
Administration
Oral (PO) Intravenous (IV)
Subtituted Benzamid
Metoclopramid NA Prechemotherapy
2-3 mg/kg IV, then
every 2-4 hours
20-40 mg (or 0.5
mg/kg) PO 4
times daily x 2-4
days
5, 10 mg
Metoclopramide is not first-line agent for acute CINV prophylaxis and should be reserved for
refractory patients. Multiple-dose regimen are required and concomitant use of diphenhydramine or
benztropine or required to prevent extrapyramidal side effects
19
